Three hypotheses will be tested. The first hypothesis is that all symptoms of cystic fibrosis (CF) stem from the absence or malfunction of a chloride channel that is gated by cAMP. The second hypothesis is that the defect resides in a kinase which regulates chloride channels, and which also might regulate other cellular properties and so contribute to the pathophysiology of CF in ways unrelated to its effects on chloride permeability. A third hypothesis is that the decrease in chloride permeability occurs in the paracellular pathway. Our specific aim is to compare ion channels in the apical membranes of endocervical columnar epithelium from control and CF subjects, using patch clamp recording techniques. We will also test comparable tissue from rabbits to see if it is a suitable model, at the single channel level, for human cervical secretion. Because fluid secretion in this tissue is under hormonal control, a cellular understanding of secretion here may eventually help clarify the persistently lower survival rate of CF women relative to men. The experiments involve 5 main steps: (1) maintain the tissue in culture; (2) obtain single channel recordings from it; (3) identify apical (and possibly basolateral) channels; (4) describe in more detail the chloride channels, including their gating characteristics; (5) repeat these steps with CF tissue and rabbit tissue.